Field of the Invention
The present invention relates to a method, a computer program and a device for determining physiological parameters related to the effective lung volume, the cardiac output, and/or the carbon dioxide content of venous blood of a subject. In particular, the invention relates to non-invasive and continuous determination of such parameters during ventilatory treatment of a patient, based on measured inspiratory and expiratory flows, and carbon dioxide content of expiration gases.
Description of the Prior Art
Cardiac output (CO) is the rate at which blood is pumped by the heart to the organs of the body. A parameter that is closely related to cardiac output is pulmonary capillary blood flow (PCBF), i.e. the alveolar blood flow. The effective (non-shunt) pulmonary capillary blood flow equals the cardiac output in case of no or neglected cardiac shunt flow. Cardiac output and effective pulmonary capillary blood flow are important measures of cardiovascular stability.
Effective lung volume (ELV) is normally defined as the volume of the lung that takes part in gas exchange, and so is an important measure of the lung function.
Monitoring parameters related to cardiac output and effective lung volume is important when the cardiovascular stability and/or the lung function is potentially threatened, such as during surgery and in critically ill patients. For example, it is often desired to monitor the effective lung volume and sometimes also cardiac output during ventilatory treatment of a patient.
There are several solutions according to prior art for non-invasive determination of parameters relating to cardiac output and/or effective lung volume. Some of these solutions make use of various variations of the carbon dioxide Fick method where the cardiac output of a patient is determined using the following basic relationship:Q=VCO2/(CvCO2−CaCO2),where Q is cardiac output or pulmonary capillary blood flow, VCO2 is the volume of carbon dioxide excreted from the body of a patient during respiration (carbon dioxide elimination), CvCO2 is carbon dioxide content of the venous blood of the patient, and CaCO2 is the carbon dioxide content of the arterial blood of the patient.
Typically, a differential form of the carbon dioxide Fick equation is used to non-invasively determine the cardiac output of the patient. Differential Fick techniques are based on the premise that cardiac output and effective pulmonary blood flow can be estimated based on the changes of other measurable parameters when a change in the effective ventilation of the patient occurs. During mechanical ventilation of a patient, such a change in effective ventilation may be effectuated e.g. by varying the degree of rebreathing of expiration gases or by changing the tidal volume, the respiratory rate or the so called insp-hold pause between inspiratory phases and expiratory phases.
EP1257201 discloses an apparatus for non-invasively measuring pulmonary capillary blood flow and cardiac output using known rebreathing techniques. In one embodiment, data on carbon dioxide elimination (VCO2) and data on carbon dioxide content of the arterial blood of the patient (CaCO2) are obtained and a correlation coefficient between the carbon dioxide elimination data and the data on the carbon dioxide content is determined. This correlation coefficient is then used to calculate at least one of the mixed venous carbon dioxide content, the pulmonary capillary blood flow, and the cardiac output.
U.S. Pat. No. 7,699,788 and WO2006047212 disclose methods for non-invasively estimating functional residual capacity or effective lung volume by obtaining carbon dioxide and flow measurements at or near the mouth of a patient. The measurements are obtained during baseline breathing and during and shortly after inducement of a change in the subject's effective ventilation. The obtained measurements are evaluated to determine the amount of time required for exhaled carbon dioxide levels to return to normal—effectively an evaluation of carbon dioxide “washout” from the subject's lungs. Conversely, carbon dioxide and flow measurements may be evaluated to determine the amount of time it takes carbon dioxide to “wash in,” or reach peak levels within, the lungs of the subject following the change in the subject's effective ventilation. Measures of the effective lung volume of the patient are then determined from relationships between parameters relating to carbon dioxide elimination and parameters relating to the carbon dioxide content of the arterial blood.
U.S. Pat. No. 6,217,524 describes a method of continuously, non-invasively determining the cardiac output of a patient. The method includes intermittently measuring the cardiac output, the volume of carbon dioxide exhaled by the patient per breath, and determining the arterial-venous gradient of the patient or a similar substantially constant value by dividing the volume of carbon dioxide exhaled by the measured cardiac output. The arterial-venous gradient or similar substantially constant value may then be employed to determine the cardiac output of the patient on a breath-by-breath basis. The carbon dioxide elimination, which is non-invasively measured as the volume of carbon dioxide exhaled by the patient per breath, is divided by the arterial-venous gradient or the substantially constant value to determine the cardiac output. The method may also include generating a signal to compensate for any non-metabolic changes in the carbon dioxide elimination, arterial-venous gradient, or other respiratory or blood gas profile measurements that may be caused by a change in ventilation or breathing of the patient.
Gedeon et al., “Pulmonary blood flow (cardiac output) and volume determined from a short breath hold using the differential Fick method”, J. CAIN. MONIT. 17:313-321 (2002), describes a non-invasive method for determining the effective lung volume of a subject using breath-holding techniques. Gedeon et al. also describes equations that relate the pulmonary capillary blood flow of the subject to the subject's effective lung volume. The method is believed to provide inaccurate data as it is based on the assumption that CO2 inflow may not be significantly affected by breath-holding, while breath-holding will cause a change in partial pressure of carbon dioxide. This assumption is inconsistent with the Fick equation, in which carbon dioxide elimination changes linearly with the partial pressure of carbon dioxide while the pulmonary capillary blood flow and the carbon dioxide content of the venous blood (CVCO2) remain constant.
Peyton et al., “Noninvasive, automated and continuous cardiac output monitoring by pulmonary capnodynamics: breath-by-breath comparison with ultrasonic flow probe”, Anesthesiology 2006 July; 105(1):72-80, describes a technique termed the capnodynamic method for breath-to-breath measurement of pulmonary blood flow from lung carbon dioxide mass balance, using measured carbon dioxide elimination and end-tidal concentration. Here, a capnodynamic equation is used to eliminate the parameter relating to carbon dioxide content of the venous blood of the patient (CvCO2) in order to obtain resulting equations from which the effective lung volume and the cardiac output can be derived iteratively. To obtain the resulting equations from which the effective lung volume and the cardiac output can be derived, measurements must be made during two substantially equal breaths (two hyperventilated or two hypoventilated breaths) and during two transient breaths (one hyperventilated breath and one hypoventilated breath). This makes the method proposed by Peyton et al. dependent on a certain ventilation pattern.
This capnodynamic method is further described in WO 2006/119546 A1. The method is herein described with reference to a continuous alternating/cyclic alveolar ventilation of a subject, with each period of alveolar ventilation at a particular level (hyperventilation or hypoventilation) constituting a half cycle. Preferably, a cycle comprises 6 to 20 breaths, typically 12 breaths; a half cycle being half of this number of breaths. The method employs a “calibration equation” which has to be solved for breaths that occur at periods in the half cycles during which washing or washout of carbon dioxide is minimized, i.e. for breaths occurring when the carbon dioxide concentration has reached a steady state following a change in effective ventilation.
U.S. Pat. No. 7,135,001 discloses a differential Fick technique for noninvasively determining the pulmonary capillary blood flow or cardiac output of a patient. The technique includes effecting a change-inducing phase in the respiration of the patient, allowing the respiration to return to normal, then immediately repeating the change-inducing phase of respiration. The technique is characterized in that the typical recovery period, where a patient's respiration is allowed to return to normal or baseline levels before again measuring respiratory carbon dioxide and flow is omitted. Thereby, the durations of the normal respiration and change-inducing phases can be abbreviated relative to the time lengths of the corresponding phases in conventional differential Fick techniques. The duration of each phase may be optimized for a patient by evaluating the patient's ventilation but should be within the interval of approximately eighteen to approximately forty-two seconds.